Kinase inhibitor roscovitine as a PB2 cap-binding inhibitor against influenza a virus replication
| Autor: | Yilu Ye, Qi Huang, Jingyan Li, Wenjiao Wu, Mingkai Feng, Jie Yang, Lizhu Chen, Shuwen Liu, Yingyuan Zhong |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Transcription Genetic viruses Therapeutic treatment Biophysics Genome Viral Virus Replication medicine.disease_cause Antiviral mechanism Antiviral Agents Biochemistry Madin Darby Canine Kidney Cells Viral Proteins 03 medical and health sciences Dogs 0302 clinical medicine Viral life cycle Roscovitine Influenza A virus medicine Animals Humans Protein Kinase Inhibitors Molecular Biology IC50 Polymerase biology Chemistry Kinase virus diseases Influenza a DNA-Directed RNA Polymerases Cell Biology Virus Internalization RNA-Dependent RNA Polymerase Virology 030104 developmental biology RNA Cap-Binding Proteins 030220 oncology & carcinogenesis biology.protein |
| Zdroj: | Biochemical and Biophysical Research Communications. 526:1143-1149 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.04.034 |
| Popis: | In this study, we examined the impact of roscovitine, a cyclin-dependent kinase inhibitor (CDKI) that has entered phase I and II clinical trials, on influenza A viruses (IAVs) and its antiviral mechanism. The results illustrated that roscovitine inhibited multiple subtypes of influenza strains dose-dependently, including A/WSN/1933(H1N1), A/Aichi/2/68 (H3N2) and A/FM1/47 (H1N1) with IC50 value of 3.35 ± 0.39, 7.01 ± 1.84 and 5.99 ± 1.89 μM, respectively. Moreover, roscovitine suppressed the gene transcription and genome replication steps in the viral life cycle. Further mechanistic studies indicated that roscovitine reduced viral polymerase activity and bound specifically to the viral PB2cap protein by fluorescence polarization assay (FP) and surface plasmon resonance (SPR). Therefore, we believed roscovitine, as a PB2cap inhibitor, was a prospective antiviral agent to be developed as therapeutic treatment against influenza A virus infection. |
| Databáze: | OpenAIRE |
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